The present invention relates to antimicrobial polymers formed by bulk polyaddition, and more specifically, to cationic polymers having quaternary backbone nitrogens formed by bulk polyaddition.
Antimicrobial agents are commonly used in personal care products to inhibit microbial growth for preventing infections and product decomposition. Most antimicrobial agents used in these products are small molecules, including anilides (e.g., triclocarban), bis-phenols (e.g., triclosan), biguanides (e.g., chlorhexidine) and quaternary ammonium compounds (e.g., cetylpyridium chloride and cetrimide). Among them, triclosan is one of the most extensively used compounds. Triclosan is present in more than 50% of consumer products including soap, deodorant, toothpaste, mouth wash, cosmetics (e.g., GARDEN BOTANIKA® Powder Foundation, Mavala Lip Base, Jason Natural Cosmetics and MOVATE® Skin Litening Cream HQ), cleaning supplies, kitchen utensils, children's toys, bedding, socks, shoes and garbage bags. It is effective against Gram-positive bacteria, while it has little activity against Pseudomonas aeruginosa (P. aeruginosa, Gram-negative bacteria) and molds. At high concentrations, triclosan is biocidal with multiple cytoplasmic and membrane targets. However, at low concentrations, it is bacteriostatic by inhibiting fatty acid synthesis. On the other hand, triclosan has cumulative and persistent effects on the skin. It was found in human milk and urine samples. At minimal concentrations of triclosan (<1 microgram/L) and chlorine (<1 mg/L), common household tap water levels, triclosan can degrade to form toxic derivatives, 2,4-dichlorophenol and 2,4,6-trichlorophenol. Moreover, in sunlight and wastewater chlorine treatment, triclosan also forms highly toxic carcinogenic dioxin-like compounds. After use, triclosan is discharged into water. Triclosan was found in 85 out of 139 streams and rivers in 30 states in the US, and is toxic to aquatic species (Kolpin, D. W., et al., “Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 1999-2000: A National Reconnaissance”, Environ. Sci. Technol. 2002, 36, 1202-1211). Triclosan was detected in sediments in a Swiss lake as far back as 1960s (Singer, H., et al., “Triclosan: Occurrence and Fate of a Widely Used Biocide in the Aquatic Environment: Field Measurements in Wastewater Treatment Plants, Surface Waters, and Lake Sediments”, Environ. Sci. Technol., 2002, 36 (23), pp 4998-5004). Triclosan resistance has been found in various strains of microbes. Therefore, the use of triclosan in consumer products is likely to be banned in Europe and in the USA.
Many strains of bacteria spores (e.g., Clostridium species), Gram-positive (e.g., mycobacteria) and Gram-negative bacteria (P. aeruginosa) have intrinsic resistance to the antimicrobial agents listed above. Moreover, these antimicrobial agents are not effective against biofilms. For example, Serratia marcescens and Burkolderia cepacia biofilms were found in disinfectant chlorhexidine solution, Pseudomonas biofilm in iodophor antiseptics and on the interior surface of polyvinyl chloride pipes used in the production of providone-iodine antiseptics. One of the major concerns is that resistant biofilms may lead to cross-resistance and co-resistance of clinically used antimicrobial agents, a potential public health risk.
Most small molecular antimicrobial agents do not physically damage the cell wall but penetrate into the target microorganism and act on specific targets. As a consequence, bacterial morphology is preserved and the bacteria can easily develop resistance. Antimicrobial peptides (AMPs) have been explored as an alternative. AMPs (e.g., magainins, alamethicin, protegrins and defensins) do not have a specific target in microbes. They interact with microbial membranes based on electrostatic interaction, thereby inducing damage to the microbial membranes by forming pores in the membranes. The physical nature of this action prevents microbes from developing resistance to AMPs. Although efforts have been made to design synthetic peptides with various structures over the last two decades, high manufacturing cost has limited their application in personal care products.
A number of cationic polymers that mimic the facially amphiphilic structure and antimicrobial functionalities of peptides have been proposed as a better approach, as they can be more easily prepared at low cost and large scale compared to peptides. For example, antimicrobial polynorbornene and polyacrylate derivatives, and pyridinium copolymers were synthesized either from amphiphilic monomers (homopolymers) or from a mixture of a cationic (hydrophilic) monomer and a hydrophobic comonomer (random copolymers). However, most antimicrobial polymers reported in the literature require several steps of synthesis that would lead to high production cost.
A need continues for more environmentally compatible antimicrobial agents used in personal care products that can rapidly kill multidrug-resistant bacteria and fungi, remove biofilms, and prevent drug resistance.